Azobisisobutyronitrile → 2-bromo-2-(4-bromo-2-fluorophenyl)-N-methylacetamide

Temperature

80 °C

A solution of 2-(4-bromo-2-fluorophenyl)-N-methylacetamide (2.479 mmol) in carbon tetrachloride (5 mL) was degassed with a stream of nitrogen for five minutes, at which point the solution was treated with N-bromosuccinimide (2.73 mmol) and azobisisobutyronitrile (0.248 mmol). The reaction vessel was purged with nitrogen and sealed, and the mixture stirred at 80° C. overnight. After stirring overnight, the reaction was cooled to room temperature. The reaction mixture was degassed again with a stream of nitrogen for three minutes and was treated with N-bromosuccinimide (0.56 mmol) and azobisisobutyronitrile (0.124 mmol). The reaction vessel was purged with nitrogen and sealed, and the mixture stirred at 80° C. for two days. The reaction was then allowed to cool and was concentrated to dryness in vacuo. Purification of the residue by silica gel chromatography (0-50% ethyl acetate/hexanes) afforded the title compound as a white solid (296 mg, 33% yield). 1H NMR (400 MHz, DMSO-d6) d ppm 2.65 (d, J=4.55 Hz, 3 H) 5.81 (s, 1 H) 7.49 (dd, J=8.59, 1.77 Hz, 1 H) 7.61 (dd, J=9.98, 1.89 Hz, 1 H) 7.72 (t, J=8.21 Hz, 1 H) 8.49 (br. s., 1 H).

1. customThe reaction vessel was purged with nitrogen
2. customsealed
3. stirringAfter stirring overnight
4. temperaturethe reaction was cooled to room temperature
5. customThe reaction mixture was degassed again with a stream of nitrogen for three minutes
6. customThe reaction vessel was purged with nitrogen
7. customsealed
8. stirringthe mixture stirred at 80° C. for two days
9. temperatureto cool
10. concentrationwas concentrated to dryness in vacuo
11. customPurification of the residue by silica gel chromatography (0-50% ethyl acetate/hexanes)

ORD record

ord-3681ce9da5b14cf39862f4da333e4944

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09084794B2